Physicochemical studies in our laboratory have shown that homogenates of invasive tumors (basal cell epithelioma, squamous cell carcinoma and melanoma) contrary to those of noninvasive tumors of similar origin, contained specific collagenolytic activity. We propose to isolate, purify, and characterize these collagenolytic systems. Purified enzymes from different tumors will be compared with each other and with normal tissue collagenase by physicochemical and immunological techniques. Nonspecific proteases which may be present will be separated and their action will be studied. The mechanism of production of these enzymes and the immunological properties of these tumor-specific enzymes will be studied in relation to the invasive nature of each tumor as determined by histopathologic manifestation. The possibility of these enzymes being tumor-specific antigens will be examined. In this project it is proposed that tissues from benign or noninvasive tumors which have potential for metastatic change may contain a collagenase precursor, zymogen or an inactive form of enzyme which may become activated during the malignant change by some mechanism to be investigated. A search for immuno-cross reacting enzyme precursors based on the competitive displacement of active enzyme from its antibody is proposed. In addition to human tumors. Shope virus papilloma and its VX-2 carcinoma will be used as an experimental model. Using the purified enzymes inhibitor studies will be carried out for possible therapeutic use.